Exploring the Role of Fibrin Gels in Enhancing Cell Migration for Vasculature Formation

Abstract

A hallmark of angiogenesis is the sprouting of endothelial cells. To replicate this event in vitro, biomaterial approaches can play an essential role in promoting cell migration. To study the capacity of a scaffold of fibrin (fibrinogen:thrombin mix) to support the movement of the endothelial cells, the migration area of spheroids formed with the HULEC cell line was measured. The cells were first allowed to form a spheroid using the hanging drop technique before being encapsulated in the fibrin gel. The cells’ migration area was then measured after two days of embedding in the fibrin gel. Various conditions affecting fibrin gel polymerization, such as different concentrations of fibrinogen and thrombin, were evaluated alongside rheology, porosity, and fiber thickness analysis to understand how these factors influenced cell behavior within the composite biomaterial. Data point toward thrombin’s role in governing fibrin gel polymerization; higher concentrations result in less rigid gels (loss tangent between 0.07 and 0.034) and increased cell migration (maximum concentration tested: 5 U/mL). The herein presented method allows for a more precise determination of the crosslinking conditions of fibrin gel that can be used to stimulate angiogenic sprouting.